Epidemiologic studies show that with smoking cessation there is only a gradual reduction in risk of lung cancer that first is evident by 5 years and remains above that of never smokers for at least 15 years. Ex-smokers remain at elevated risk for many years after quitting and form an important reservoir for cancer development. We hypothesize that persistence of preneoplastic markers after smoking cessation may identify those ex-smokers who are still at risk of lung cancer. Our specific aims are 1) To assess the degree and time course of reversion of preneoplastic markers (sputum cytology atypia and urine bombesin-like peptide) to normal after smoking cessation in smokers who are high risk for lung cancer. 2) To characterize individuals who do not show reversion of these markers to normal after smoking cessation. 3) To establish a bank of sputum cytology samples from this cohort of high risk subjects followed prospectively before and after smoking cessation that can be used for rapid pilot testing of new lung cancer markers. To accomplish these aims, we will follow a cohort of 220 smokers with COPD and at least mild sputum cytology atypia before and for 12 months after a smoking cessation intervention using behavioral strategies and transdermal nicotine. We will compare sputum cytology results and urine bombesin-like peptide levels between continued smokers and successful quitters. The results of this project will allow application of chemoprevention efforts to targeted groups of ex-smokers who remain at high risk for lung cancer and will create a tissue bank that will be a valuable resource for rapid testing of new lung cancer markers in the future.